90 research outputs found

    Uniqueness of the gauge invariant action for cosmological perturbations

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    In second order perturbation theory different definitions are known of gauge invariant perturbations in single field inflationary models. Consequently the corresponding gauge invariant cubic actions do not have the same form. Here we show that the cubic action for one choice of gauge invariant variables is unique in the following sense: the action for any other, non-linearly related variable can be brought to the same bulk action, plus additional boundary terms. These boundary terms correspond to the choice of hypersurface and generate extra, disconnected contributions to the bispectrum. We also discuss uniqueness of the action with respect to conformal frames. When expressed in terms of the gauge invariant curvature perturbation on uniform field hypersurfaces the action for cosmological perturbations has a unique form, independent of the original Einstein or Jordan frame. Crucial is that the gauge invariant comoving curvature perturbation is frame independent, which makes it extremely helpful in showing the quantum equivalence of the two frames, and therefore in calculating quantum effects in nonminimally coupled theories such as Higss inflation.Comment: 27 page

    Post COVID-19 Pandemic Increased Detection of Mycoplasma Pneumoniae in Adults Admitted to the Intensive Care

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    Background: Mycoplasma pneumoniae (M. pneumoniae) infections can progress to severe respiratory complications, necessitating intensive care treatment. Recent post COVID-19 pandemic surges underscore the need for timely diagnosis, given potential diagnostic method limitations. Methods: A retrospective case series analysis was conducted on M. pneumonia PCR-positive patients admitted to two Dutch secondary hospitals’ ICUs between January 2023 and February 2024. Clinical presentations, treatments, outcomes, and mechanical ventilation data were assessed. Results: Seventeen ICU-admitted patients were identified, with a median age of 44 years, primarily due to hypoxia. Non-invasive ventilation was effective for most, while five required invasive mechanical ventilation. None of the patients required extracorporeal membrane oxygenation. No fatalities occurred. Post-PCR, treatment was adjusted to doxycycline or azithromycin; seven received steroid treatment. Discussion: Increased ICU admissions for M. pneumoniae infection were observed. Diverse clinical and radiological findings emphasize heightened clinical awareness. Early molecular diagnostics and tailored antibiotic regimens are crucial since beta-lactam antibiotics are ineffective. Conclusion: This study highlights the escalating challenge of severe M. pneumoniae infections in ICUs, necessitating a multifaceted approach involving accurate diagnostics, vigilant monitoring, and adaptable treatment strategies for optimal patient outcomes.</p

    Sexual orientation and symptoms of common mental disorder or low wellbeing: combined meta-analysis of 12 UK population health surveys

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    Background Previous studies have indicated increased risk of mental disorder symptoms, suicide and substance misuse in lesbian, gay and bisexual (LGB) adults, compared to heterosexual adults. Our aims were to determine an estimate of the association between sexual orientation identity and poor mental health and wellbeing among adults from 12 population surveys in the UK, and to consider whether effects differed for specific subgroups of the population. Methods Individual data were pooled from the British Cohort Study 2012, Health Survey for England 2011, 2012 and 2013, Scottish Health Survey 2008 to 2013, Longitudinal Study of Young People in England 2009/10 and Understanding Society 2011/12. Individual participant meta-analysis was used to pool estimates from each study, allowing for between-study variation. Results Of 94,818 participants, 1.1 % identified as lesbian/gay, 0.9 % as bisexual, 0.8 % as ‘other’ and 97.2 % as heterosexual. Adjusting for a range of covariates, adults who identified as lesbian/gay had higher prevalence of common mental disorder when compared to heterosexuals, but the association was different in different age groups: apparent for those under 35 (OR = 1.78, 95 % CI 1.40, 2.26), weaker at age 35–54.9 (OR = 1.42, 95 % CI 1.10, 1.84), but strongest at age 55+ (OR = 2.06, 95 % CI 1.29, 3.31). These effects were stronger for bisexual adults, similar for those identifying as ‘other’, and similar for 'low wellbeing'. Conclusions In the UK, LGB adults have higher prevalence of poor mental health and low wellbeing when compared to heterosexuals, particularly younger and older LGB adults. Sexual orientation identity should be measured routinely in all health studies and in administrative data in the UK in order to influence national and local policy development and service delivery. These results reiterate the need for local government, NHS providers and public health policy makers to consider how to address inequalities in mental health among these minority groups

    Crime among irregular immigrants and the influence of internal border control

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    Both the number of crime suspects without legal status and the number of irregular or undocumented immigrants held in detention facilities increased substantially in theNetherlands between 1997 and 2003. In this period, theDutch state increasingly attempted to exclude irregular immigrants from the formal labour market and public provisions. At the same time the registered crime among irregular migrants rose. The 'marginalisation thesis' asserts that a larger number of migrants have become involved in crime in response to a decrease in conventional life chances. Using police and administrative data, the present study takes four alternative interpretations into consideration based on: 1) reclassification of immigrant statuses by the state and redefinition of the law, 2) criminal migration and crossborder crime, 3) changes in policing, and 4) demographic changes. A combination of factors is found to have caused the rise in crime, but the marginalisation thesis still accounts for at least 28%. These findings accentuate the need for a more thorough discussion on the intended and unintended consequences of border control for immigrant crime

    Attitudes of Dutch intensive care unit clinicians towards oxygen therapy

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    BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly

    Effects of a defective ERAD pathway on growth and heterologous protein production in Aspergillus niger

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    Endoplasmic reticulum associated degradation (ERAD) is a conserved mechanism to remove misfolded proteins from the ER by targeting them to the proteasome for degradation. To assess the role of ERAD in filamentous fungi, we have examined the consequences of disrupting putative ERAD components in the filamentous fungus Aspergillus niger. Deletion of derA, doaA, hrdC, mifA, or mnsA in A. niger yields viable strains, and with the exception of doaA, no significant growth phenotype is observed when compared to the parental strain. The gene deletion mutants were also made in A. niger strains containing single- or multicopies of a glucoamylase–glucuronidase (GlaGus) gene fusion. The induction of the unfolded protein response (UPR) target genes (bipA and pdiA) was dependent on the copy number of the heterologous gene and the ERAD gene deleted. The highest induction of UPR target genes was observed in ERAD mutants containing multiple copies of the GlaGus gene. Western blot analysis revealed that deletion of the derA gene in the multicopy GlaGus overexpressing strain resulted in a 6-fold increase in the intracellular amount of GlaGus protein detected. Our results suggest that impairing some components of the ERAD pathway in combination with high expression levels of the heterologous protein results in higher intracellular protein levels, indicating a delay in protein degradation

    Rational Diversification of a Promoter Providing Fine-Tuned Expression and Orthogonal Regulation for Synthetic Biology

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    Yeast is an ideal organism for the development and application of synthetic biology, yet there remain relatively few well-characterised biological parts suitable for precise engineering of this chassis. In order to address this current need, we present here a strategy that takes a single biological part, a promoter, and re-engineers it to produce a fine-graded output range promoter library and new regulated promoters desirable for orthogonal synthetic biology applications. A highly constitutive Saccharomyces cerevisiae promoter, PFY1p, was identified by bioinformatic approaches, characterised in vivo and diversified at its core sequence to create a 36-member promoter library. TetR regulation was introduced into PFY1p to create a synthetic inducible promoter (iPFY1p) that functions in an inverter device. Orthogonal and scalable regulation of synthetic promoters was then demonstrated for the first time using customisable Transcription Activator-Like Effectors (TALEs) modified and designed to act as orthogonal repressors for specific PFY1-based promoters. The ability to diversify a promoter at its core sequences and then independently target Transcription Activator-Like Orthogonal Repressors (TALORs) to virtually any of these sequences shows great promise toward the design and construction of future synthetic gene networks that encode complex “multi-wire” logic functions
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